PubMed Health⌕ Search

Biomedical subjects

A Imperato

Publications and source records attributed to A Imperato.

At least 55 records · Page 3Linked to original sources
PubMed1994

Neuroleptics cause stimulation of dopamine D1 receptors and their desensitization after chronic treatment.

Recent evidence indicates that the neuroleptic-induced increase of in vivo acetylcholine output in the striatum does not depend on the relief of cholinergic neurons from the inhibitory control by dopamine, but on increased dopamine output onto dopamine D1 receptors. The present microdialysis study was aimed at finding if the neuroleptic-induced increase in striatal acetylcholine release persists after chronic treatment, and how it is correlated with dopamine output. Rats were chronically treated with the dopamine D2 receptor antagonists, haloperidol and (-)-sulpiride (0.5 mg/kg and 50 mg/kg i.p., respectively, daily, for 30 days). The stimulant effect of both neuroleptics on striatal dopamine release persisted unaltered throughout the chronic treatment (by about 100% over basal values). In contrast, the enhancing effects of haloperidol and (-)-sulpiride on striatal acetylcholine release remained unchanged up to day 12 of treatment. Thereafter, tolerance developed, so that both neuroleptics became totally ineffective on day 30 of treatment. Both on day 1 and 30, the neuroleptic-induced dopamine release was reversed by gamma-butyrolactone (gamma-hydroxybutyric acid lactone), suggesting that this effect is mediated by enhanced neuronal activity. On day 1 and day 10, the neuroleptic-induced acetylcholine release was antagonized by the blockade of dopamine D1 receptors with SCH 39166 (trans-(-)-(6aS,13bR)-11-chloro-6,6a,7,8,9,13b- hexahydro-7-methyl-5H-benzo[d]napht[2,1-b]azepine-12-ol, hydrochloride) (0.5 mg/kg i.p.). SKF 38393 (1-phenyl-2,3,4,5-tetrahydro-(1H)-3- benzazepine-7,8-diol hydrochloride) (5 mg/kg i.p.) increased acetylcholine release by about 50% in control rats and in rats treated with (-)-sulpiride or haloperidol for up to 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Differential effects of abecarnil on basal release of acetylcholine and dopamine in the rat brain.

Abecarnil (0.1-1 mg/kg i.p.), a new anxioselective and anticonvulsant ligand of benzodiazepine receptors, like diazepam (2.5-10 mg/kg i.p.) inhibited in a dose-dependent manner the basal release of acetylcholine in the hippocampus of freely moving rats. In contrast, whereas diazepam inhibited the basal output of dopamine in the prefrontal cortex, abecarnil had no such effect. The effects of both abecarnil and diazepam were antagonized by prior treatment with flumazenil at a dose (1 mg/kg i.p.) that per se had no effect on acetylcholine or dopamine release. The results suggest that abecarnil has different intrinsic efficacies at gamma-aminobutyric acid type A (GABAA) receptors involved in the regulation of acetylcholine release in the hippocampus and dopamine release in the prefrontal cortex, two brain areas important in cognitive function and emotional state, respectively.

Acetylcholine↗
PubMed1994

The benzodiazepine receptor antagonist flumazenil increases acetylcholine release in rat hippocampus.

The benzodiazepine receptor antagonist flumazenil (2.5-20 mg/kg i.p.) increased acetylcholine (ACh) release by up to 85% in the hippocampus of freely moving rats. In contrast, the benzodiazepine receptor full agonist diazepam (2.5-10 mg/kg i.p.) decreased ACh release up to a maximum of 45% in the same brain area. Injection of flumazenil (10 pmol) or diazepam (10 pmol) into the medial septum increased (95%) or reduced (50%), respectively, ACh release in the hippocampus. The maximum effect produced by those drugs was of the same magnitude as that observed after systemic injection. The changes in hippocampal cholinergic function elicited by activation and blockade of benzodiazepine receptors in the medial septum may thus play a crucial role in the alterations of the cognitive processes elicited by benzodiazepine receptor ligands.

Acetylcholine↗
PubMed1994

Co-dergocrine (Hydergine) regulates striatal and hippocampal acetylcholine release through D2 receptors.

The effect of Co-dergocrine (Hydergine) on acetylcholine (ACh) release in the striatum and hippocampus has been studied by means of brain microdialysis and compared to the effect of SKF 38393 and of LY 171555 selective D1 and D2 dopamine (DA) receptor agonists, respectively. Co-dergocrine (1 and 5 mg kg-1 i.p.) as well as LY 171555 (0.2 and 0.5 mg kg-1 i.p.) decreased the extracellular concentration of ACh in the striatum, whereas SKF 38393 (5 and 10 mg kg-1 i.p.) increased it. On the other hand, Co-dergocrine (1 and 5 mg kg-1), LY 171555 (0.2 and 0.5 mg kg-1) and SKF 38393 (5 and 10 mg kg-1) increased ACh release in the hippocampus in a dose-dependent way. These results show that Co-dergocrine, which is widely used in the treatment of senile mental decline, enhances the release of ACh in the hippocampus in a similar manner to both D1 and D2 DA agonists. This effect might be relevant for the amelioration of cognitive processes. Moreover, our results which demonstrate that Co-dergocrine is able to decrease the release of ACh in the striatum, as are selective D2 agonists, suggest that Co-dergocrine may have a potential therapeutic benefit in Parkinsonian dementia.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Effects of subchronic minaprine on dopamine release in the ventral striatum and on immobility in the forced swimming test.

Subchronic (5 mg/kg daily for 9 consecutive days) but not acute minaprine treatment enhanced in vivo dopamine release in the limbic part of the striatum of rats as revealed by intracerebral microdialysis. Moreover, the same subchronic treatment with minaprine reduced immobility in the forced swimming test. The anti-immobility effect of minaprine was not evident after a single injection of the antidepressant. Finally, the subchronic treatment with minaprine was devoid of effects in an activity test. These results suggest that enhanced dopaminergic transmission may contribute to the pharmacological and clinical profile of this drug.

Animals↗
PubMed1994

Does dopamine exert a tonic inhibitory control on the release of striatal acetylcholine in vivo?

The role of dopamine transmission on striatal acetylcholine release was investigated by using brain microdialysis. Blockade of dopamine D2 receptors with (-)-sulpiride or haloperidol increased acetylcholine release to a maximum of 80% (after 50 and 0.5 mg/kg, respectively). This effect was prevented by blockade of dopamine D1 receptors with 0.5 mg/kg SCH 39166 or 0.1 mg/kg SCH 23390, or by depletion of dopamine stores after 5 mg/kg reserpine + 150 mg/kg alpha-methyltyrosine. Treatment with SCH 39166, SCH 23390 or reserpine + alpha-methyltyrosine reduced acetylcholine release by about a maximum of 30%. Stimulation of dopamine D2 receptors with LY 171555 (quinpirole) at a low, sedative dose (0.05 mg/kg) reduced acetylcholine release by about 30% with no further reduction at higher doses up to 1 mg/kg. Moreover, LY 171555 (0.1 mg/kg) given to SCH 39166 (0.5 mg/kg)- or SKF 38393 (20 mg/kg)-pretreated rats did not decrease acetylcholine release, suggesting that its effect is through a dopamine D1 receptor-mediated mechanism. In contrast, in dopamine-depleted rats, LY 171555 0.1 mg/kg became more effective in decreasing acetylcholine release (about 70%) also after SCH 39166 (0.5 mg/kg) pretreatment (about 80%), thus acting independently of dopamine D1 receptor mechanisms. These results indicate that, in normal circumstances, endogenous dopamine facilitates striatal acetylcholine release through dopamine D1 receptors. The results argue against the commonly accepted view that dopamine D2 receptors exert a tonic inhibitory control on acetylcholine release. Moreover, they suggest that dopamine D2 receptors, in circumstances of dopamine depletion, may exert an inhibitory control on acetylcholine release independent of dopamine D1 receptor mechanisms.

Acetylcholine↗
PubMed1993

Stimulation of both dopamine D1 and D2 receptors facilitates in vivo acetylcholine release in the hippocampus.

The effect of selective D1 and D2 dopamine (DA) receptor agonists and of a mixed D1/D2 agonist on hippocampal acetylcholine (ACh) release was investigated. LY 171555 (0.5 and 1 mg/kg, i.p.), SKF 38393 (1 to 10 mg/kg, i.p.), CY 208-243 (0.2 mg/kg, i.p.) and apomorphine (0.5 to 2 mg/kg, i.p.), at doses stimulating rat behavior, were found to increase the output of ACh in the hippocampus. Maximal increase was observed after LY 171555 1 mg/kg, SKF 38393 10 mg/kg, CY 208-243 2 mg/kg and apomorphine 2 mg/kg (85, 90, 87 and 210%, respectively). The enhancement of ACh release induced by either SKF 38393 (10 mg/kg) or LY 171555 (1 mg/kg) was prevented by the blockade of D1 receptors with SCH 23390 (0.1 mg/kg, s.c.). Co-administration of maximally active doses of LY 171555 (1 mg/kg) and SKF 38393 (10 mg/kg) produced an additive effect (about 200%). In contrast to the findings with high doses, low, presynaptic doses of LY 171555 and apomorphine reduced ACh output. Maximal reduction was observed after 0.05 mg/kg for both drugs, (43 and 52%, respectively). These results show that activation of dopaminergic transmission either at D1 and/or at D2 receptors enhances ACh output in the hippocampus.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Effects of cocaine and amphetamine on acetylcholine release in the hippocampus and caudate nucleus.

The role of dopamine in the control of hippocampal acetylcholine release was evaluated by using in vivo microdialysis. The effects of the two psychostimulants, cocaine and d-amphetamine, were studied on acetylcholine release in the hippocampus and compared to effects observed in the caudate nucleus. Administration of cocaine (10 and 20 mg/kg i.p.) increased acetylcholine release by 130 and 190% in the hippocampus, whereas in the caudate nucleus the enhancement was 51 and 80% over basal values, respectively. After the injection of d-amphetamine (1 and 2 mg/kg i.p.) the enhancement of acetylcholine release was 110 and 210% in the hippocampus whereas it was 35 and 54%, respectively, in the caudate nucleus. As observed in the caudate nucleus, pretreatment with the dopamine D1 receptor antagonist, SCH 23390, antagonized the cocaine- and amphetamine-induced increase in hippocampal acetylcholine release. These results show that cocaine and d-amphetamine, by increasing dopaminergic transmission, enhance the extracellular concentrations of acetylcholine in both brain areas. The relative enhancement in the hippocampus was far greater than that in the caudate nucleus, suggesting that dopaminergic control of cholinergic function differs in these two brain areas. The results also suggest that endogenous dopamine, by facilitating the release of acetylcholine in the hippocampus, may participate in the regulation of hippocampal cognitive processes.

Acetylcholine↗
PubMed1993

Inhibition of hippocampal acetylcholine release by benzodiazepines: antagonism by flumazenil.

Diazepam (2.5-10 mg/kg i.p.) and midazolam (2.5-10 mg/kg i.p.) decreased acetylcholine release in the hippocampus of freely moving rats. This effect was antagonized by pretreatment with flumazenil (1 mg/kg i.p.). These results show that activation of benzodiazepine receptors reduces the in vivo release of acetylcholine in the hippocampus, suggesting that the septo-hippocampal cholinergic system, which has a major role in the regulation of cognitive functions, is under inhibitory control exerted by gamma-aminobutyrate (GABA) neurons.

Acetylcholine↗
PubMed1993

Repeated stressful experiences differently affect the time-dependent responses of the mesolimbic dopamine system to the stressor.

The increase in mesolimbic dopamine (DA) release observed during the first 40 min of 120 min restraint in naive rats is not evident in repeatedly stressed animals (daily 60 min restraint, for 5 days). However, repeatedly stressed rats show a significant decrease in DA release from 80 min of restraint onwards which is not observable in naive rats. These results indicate that repeated stressful experiences do not produce habituation but alter the response of mesolimbic DA system to the stressor. Moreover, they point to a possible neuronal mechanism underlying stress-induced depression.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Evidence that neuroleptics increase striatal acetylcholine release through stimulation of dopamine D1 receptors.

The relative role of D1 and D2 dopamine receptors in the neuroleptic-induced increase of striatal acetylcholine (ACh) release was investigated using brain microdialysis in freely moving rats. Administration of (-)-sulpiride, haloperidol and clozapine, produced a dose-related increase in ACh release in the striatum. Maximal increase by 52, 45 and 73% over basal values was produced by the dose of 20, 0.25 and 10 mg/kg i.p. of (-)-sulpiride, haloperidol and clozapine, respectively. Administration of the D1 receptor antagonist SCH 23390 (0.1 mg/kg s.c.) decreased ACh output by 30%, completely suppressed the stimulant effect of (-)-sulpiride and haloperidol and only modestly reduced that of clozapine. The inhibitory effect of SCH 23390 vs. (-)-sulpiride or haloperidol-induced ACh output was shared by SCH 39166 (1 mg/kg i.p.), another specific D1 receptor antagonist. On the other hand, SCH 23390 (0.1 mg/kg s.c.) was ineffective in reducing atropine-induced increase in ACh release. A combined treatment with reserpine (5 mg/kg i.p.) and alpha-methyltyrosine (150 mg/kg i.p.), 6 h beforehand, prevented the enhancement of ACh release induced by both (-)-sulpiride and haloperidol, whereas only reduced that by clozapine. The results indicate that neuroleptics increase striatal ACh release by enhancing endogenous extracellular dopamine acting on D1 receptors, and suggest that these receptors play a major physiological role in controlling ACh release in the striatum.

Acetylcholine↗
PubMed1992

Cocaine releases limbic acetylcholine through endogenous dopamine action on D1 receptors.

Cocaine (10 and 20 mg/kg i.p.) enhanced the extracellular concentration of acetylcholine (ACh) in the ventral striatum of freely moving rats. The enhancement was prevented both by dopamine (DA) D1 receptor blockade with SCH 23390 (0.1 mg/kg s.c.) and by depletion of endogenous DA after coadministration of reserpine (5 mg/kg i.p.) and alpha-methyltyrosine (alpha-MT) (150 mg/kg i.p.). In contrast, blockade of DA D2 receptors with (-)-sulpiride (20 mg/kg i.p.) did not prevent the cocaine-induced increase in ACh release. These results indicate that the cocaine-induced stimulation of ACh release is mediated by an action of DA on D1 receptors, and suggest that the enhancement of ACh release might play a functional role in the central effects of cocaine. Moreover, DA depletion after reserpine + alpha-MT or D1 receptor blockade with SCH 23390 led to a comparable decrease of baseline ACh release, suggesting that striatal cholinergic interneurons are under D1 receptor-mediated facilitatory dopaminergic control.

Acetylcholine↗
PubMed1992

Repeated stressful experiences differently affect limbic dopamine release during and following stress.

The effects of repeated restraint stress exposures (daily 60 min, for 6 days) on extracellular dopamine in the nucleus accumbens, during and after the stress experience, have been investigated in rats by in vivo microdialysis. On the first day, restraint increased dopamine release during the first 40 min followed by a return to basal levels (50-60 min later). As soon as restraint ceased and the rats were set free, there was another increase in dopamine release lasting 40 min. On the second and third day, restraint produced only a slight increase in dopamine release, while no significant changes were evident from the fourth to the sixth day. By contrast, from the second to the sixth day the increase in dopamine release observed once rats were freed, was unchanged in comparison to the first day. The present results show that the activation of the mesolimbic dopaminergic system induced by aversive stimuli adapts to repeated experiences differently from that produced by pleasurable events, suggesting that aversive and rewarding experiences involve different neural systems.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Chronic cocaine alters limbic extracellular dopamine. Neurochemical basis for addiction.

The extracellular concentration of dopamine in the ventral striatum was measured daily by means of brain microdialysis. Chronic cocaine (10 mg/kg twice daily) altered the dopamine output compared to that in vehicle-injected rats, inducing a pronounced increase in the first 3 days followed by a clear-cut decrease. This reduction in the output of dopamine during chronic cocaine as well as during withdrawal may be neurochemical substrate for the addictive properties of cocaine.

Animals↗
PubMed1992

L-alpha-glycerylphosphorylcholine antagonizes scopolamine-induced amnesia and enhances hippocampal cholinergic transmission in the rat.

The effects of L-alpha-glycerylphosphorylcholine (alpha-GPC) on scopolamine-induced memory impairment and on brain acetylcholine (ACh) synthesis and release were investigated in rats. Oral administration of alpha-GPC 3 h before the behavioural test prevented the learning impairment induced by scopolamine given 30 min before the acquisition of a passive avoidance response. Similarly, retrograde amnesia induced by scopolamine, given immediately after acquisition training, was also completely reversed by the drug. These effects were dose-dependent with a maximum at 300 mg/kg. The mechanism of action of this compound was investigated by measuring hippocampal ACh synthesis and release both in vivo by means of the microdialysis technique and in vitro in tissue slices. alpha-GPC dose dependently increased ACh release with a maximum at 300 mg/kg. In addition, i.v. injection of [14C]alpha-GPC resulted in [14C]ACh formation. The data suggest that the behavioural effects of alpha-GPC may be related to its property to increase hippocampal ACh synthesis and release.

Acetylcholine↗
PubMed1991

Acute stress induces time-dependent responses in dopamine mesolimbic system.

Exposure to either restraint or footshock (3-60 min) induced similar biphasic alterations of 3-methoxytyramine (3-MT) concentrations (initial increase followed by decrease below control levels) in the nucleus accumbens septi (NAS) of mice, as revealed by tissue analysis. The only difference between the two stressors was the earlier onset of the decrease phase in the restrained mice. In both stressful conditions acid metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) increased throughout stress, while no significant changes in dopamine (DA) concentrations occurred. These data suggest biphasic alteration of DA release during prolonged stress exposure. The analysis of release in restrained conscious rats by in vivo microdialysis (10-240 min) showed a similar biphasic DA evolution (initial increase followed by decrease below baseline levels) in the NAS. The only difference from the previous experiment was the delayed onset of the decrease phase. Similar changes in DOPAC and HVA were also evident. Moreover, freed rats showed an immediate increase of DA release over baseline levels, also indicating that depletion of the neurotransmitter cannot account for the reduction of released DA. Taken together, these results support the hypothesis that biphasic alteration of DA transmission in the mesolimbic system is a general response to stress and suggest that the initial increase of DA release represents an arousal response while the subsequent decrease in DA release may be related to coping failure.

3,4-Dihydroxyphenylacetic Acid↗